In 2007, lung cancer will be the number one cancer killer in the US with the identification of an estimated 213,380 new lung cancer cases. Roughly one-quarter of these patients will be considered candidates for potentially curative surgical resection. The extent of tissue removed during surgical resection of the tumor is minimized to preserve as much lung function as possible and reduce morbidity. Unfortunately, local recurrence following limited resection is significantly increased, and doubles to 16% even in patients with early stage lung cancer. While radiation and chemotherapy are commonly utilized as adjuvant therapies for more advanced primary cancers, use as a preventative therapy to decrease recurrence is administered only in selected cases. This is a consequence of the often severe side-effects associated with these treatments and the inability to accurately predict in which patients the benefits would warrant the additional morbidity. In this phase 1 proposal, FIFth Base proposes to develop and evaluate paclitaxel-loaded polyester-carbonate copolymer films for localized delivery of anticancer agents for preventing local recurrence in an in vivo model of lung cancer. The three Specific Aims are: SPECIFIC AIM 1: Prepare and characterize paclitaxel-loaded poly(ester-co-carbonate) films and their anti-proliferative response in vitro. SPECIFIC AIM 2: Obtain safety data on the poly(carbonate-co-ester) scaffold necessary for the submission of an Investigational Device Exemption with the FDA, required for human use. SPECIFIC AIM 3: Evaluate anti-cancer activity of paclitaxel-loaded films in subcutaneous and recurrence tumor models in vivo. Successful completion of these Aims will produce a prototype delivery device that: (1) delivers drug in a sustained and controlled manner directly to the site of disease (i.e. site of resection); (2) that maintains mechanical integrity throughout its functional life; (3) that minimizes the side effects associated with intravenously-administered chemotherapy; (4) that is compatible with current surgical techniques; (5) that allows for sufficient healing of the tissue at/near the resection margins, and (6) that elicits minimal or no antigenic response. PUBLIC HEALTH RELEVANCE:In 2007, lung cancer will be the number one cancer killer in the US with the identification of an estimated 213,380 new lung cancer cases. Roughly one-quarter of these patients will be considered candidates for potentially curative surgical resection. The extent of tissue removed during surgical resection of the tumor is minimized to preserve as much lung function as possible and reduce morbidity. Unfortunately, local recurrence following limited resection is significantly increased, and doubles to 16% even in patients with early stage lung cancer. While radiation and chemotherapy are commonly utilized as adjuvant therapies for more advanced primary cancers, use as a preventative therapy to decrease recurrence is administered only in selected cases. This is a consequence of the often severe side-effects associated with these treatments and the inability to accurately predict in which patients the benefits would warrant the additional morbidity. We are developing a drug delivery device that can be fixated along resection margins for the prevention of local recurrence. The ability to inhibit recurrence of malignant disease through local delivery while minimizing systemic exposure to toxic anticancer agents will ultimately lead to the first standard of care for prevention of recurrence in early stage lung cancer patients. [unreadable] [unreadable] [unreadable]